Methods for preparing a heat exchange catheter system and for heating and/or cooling a subject&#39;s body

ABSTRACT

Closed loop heat exchange catheter systems and methods for preparing and using such systems wherein a reservoir or fluid bag is connected to the catheter system and used for at least priming of the system with a heat exchange fluid.

RELATED APPLICATIONS

This is a continuation of U.S. patent application Ser. No. 12/853,864filed Aug. 10, 2010, which is a continuation of U.S. patent applicationSer. No. 11/931,463 filed Oct. 31, 2007 and now issued as U.S. Pat. No.7,771,460, which is a continuation of Ser. No. 11/724,075 filed Mar. 13,2007 and now issued as U.S. Pat. No. 7,494,504, which is a which is acontinuation of U.S. patent application Ser. No. 10/626,007 filed Jul.24, 2003 and now issued as U.S. Pat. No. 7,217,282, which is acontinuation of Ser. No. 09/138,830 filed Aug. 24, 1998. Thisapplication does not claim priority prior to Aug. 24, 1998.

FIELD OF THE INVENTION

The present invention generally relates to the selective modificationand control of a patient's body temperature, and to the regulation ofthe temperature of a fluid that is to be delivered to a specific targetlocation within a body structure. More particularly, the inventionprovides methods and apparatus for treating or inducing hypothermia orhyperthermia by inserting a catheter into a blood vessel of the patientand selectively transferring heat to or from blood flowing through thevessel, and for altering the temperature of a fluid that is to bedelivered to the target location while the fluid is within the patient.

The present invention further relates to the selective modification andcontrol of whole body temperature and the temperature of selected targetregions of the body such as the brain. More particularly, the inventionis directed to methods and apparatus for lowering the temperature of thebrain by using heat transfer regions of a heat transfer catheter to coolfluids in contact with, or circulating in, around, or leading to thebrain region to provide regional hypothermia and temperature control.

BACKGROUND OF THE INVENTION

Under ordinary circumstances, the thermal regulatory system of the humanbody maintains a near constant temperature of about 37° C. (98.6° F.).Heat lost to the environment is precisely balanced by internal heatproduced within the body.

Hypothermia is a condition of abnormally low body temperature generallycharacterized by a core body temperature of 35° C. or less, and may befurther clinically defined according to its severity. For example, abody core temperature within the range of 32° C. to 35° C. may bedescribed as mild hypothermia, 30° C. to 32° C. as moderate, 24° C. to30° C. as severe, and a body temperature of less than 24° C. mayconstitute profound hypothermia. Although the above ranges may provide auseful basis for discussion, they are not absolutes and definitions varywidely as indicated in the medical literature.

Hyperthermia may be defined as a condition of abnormally high bodytemperature, and may be the result from exposure to a hot environment orsurroundings, overexertion, or fever. Body core temperatures may rangefrom 38° C. to 41° C. due to conditions such as fever, and may besubstantially higher in cases of exposure and overexertion. Likehypothermia, hyperthermia is a serious condition that can be fatal.

Although both hypothermia and hyperthermia may be harmful and requiretreatment in some case, in other cases hyperthermia or hypothermia, andparticularly hypothermia, may be therapeutic or otherwise advantageous,and therefore may be intentionally induced. For example, periods ofcardiac arrest in the setting of myocardial infarction and heart surgerycan produce brain damage or other nerve damage. Hypothermia isrecognized in the medical community as an accepted neuroprotectantduring cardiovascular surgery and therefore a patient is often kept in astate of induced hypothermia during cardiovascular surgery. Likewise,hypothermia is sometimes induced as a neuroprotectant duringneurosurgery. Hypothermia may also be beneficial in other situations,for example, for victims of head trauma, spinal trauma, brain attack(also sometimes called stroke), spinal surgery or surgery where bloodflow may be interrupted or compromised to the brain or spinal cord suchas aneurysm repair, as well as other types of surgery whereneuroprotection is desirable.

Neural tissue, that is all tissue of the nervous system such as thebrain or spinal cord, is particularly subject to damage by vasculardisease processes including, but not limited to ischemic or hemorrhagicstroke, blood deprivation for any reason, including cardiac arrest,intracerebral hemorrhage and head trauma. In each of these instances,damage to brain tissue may occur because of ischemia, pressure, edema orother processes resulting in a loss of cerebral function and permanentneurological deficits. Lowering the brain temperature may conferneuroprotection through several mechanisms including the blunting ofpost-insult elevation of neurotransmitters such as glutamate, reductionof cerebral metabolic rate, moderation of intracellular calcium,prevention of intracellular protein synthesis inhibition, and reductionof free radical formation as well as other enzymatic cascades and evengenetic responses. Thus intentionally induced hypothermia may preventsome of the damage to brain or other neurological tissue during surgeryor as a result of stroke, intracerebral hemorrhage and trauma.

Treatment of stroke in particular is a possibly therapeutic use ofintentionally induced hypothermia. Stroke (sometimes called brainattack) is a severely debilitating and complex disease that results fromthe blockage (ischemic stroke) or rupture (hemorrhagic stroke) of ablood vessel within or leading to the brain region. During a stroke,brain cells are damaged either by a lack of oxygen or by increasedpressure. These events can eventually result in death and necrosis ofbrain tissue. In general, at least one goal in the therapeuticintervention for stroke is to preserve the function of as much braintissue as possible. However, current medical treatment for stroke islargely supportive in nature. Newer treatments, for exampleclot-dissolving drugs, are available but may be only suitable fortreatment of ischemic strokes and must generally be used shortly (withinseveral hours) of the initial stroke symptoms to avoid side effectsrelated to bleeding within the brain. In practice, it has been difficultto treat strokes within this time window since patients often do notarrive at a medical facility until several hours after the onset of astroke. As a result, most strokes are not aggressively treated withmedical therapy. A treatment to prolong this time window, and to protectbrain cells from death, would have a profound impact on patient care.

Experimental studies of ischemia have shown reduction in infarcted braintissue volume in animals treated with hypothermia during or shortlyafter a stroke or ischemic insult. It is therefore believed that theapplication of hypothermia to a patient who is suffering or has recentlysuffered a stroke may be beneficial.

Despite the acceptance of hypothermia as a neuroprotectant, it has notbeen widely used outside of the surgical setting. Additionally, mostcurrent practices attempt to provide hypothermia to the brain byinducing whole body hypothermia through systemic treatment. However,whole body hypothermia presents numerous difficulties and is cumbersometo implement in a patient who is not under general anesthesia. Loweringthe systemic temperature of a patient not only takes a significantamount of time, but also subjects the patient to deleterious effects ofhypothermia including cardiac arrhythmias, coagulation problems,increased susceptibility to infections, and problems of discomfort suchas profound shivering.

Control of the body's temperature, for example, to maintain normothermia(usually 37° C.), is often desirable. For example, in a patient undergeneral anesthesia, the body's normal temperature regulating mechanismsmay not be fully functioning, and the anesthesiologist may be requiredto artificially control the patient's body temperature. Similarly, apatient may lose an extraordinary amount of heat to the environment, forexample, during major surgery, and the patient's unaided body may not beable to generate sufficient heat to compensate for the heat lost. Adevice and method for controlling body temperature, for example byadding heat to maintain normothermia, would be desirable.

Particularly in the surgical setting, it has sometimes been the casethat blood or other fluid was heated or cooled outside a patient's bodyand introduced into the body to heat or cool the body or some targetlocation within the body. However, heating or cooling fluids outside ofthe patient may be cumbersome and require elaborate equipment. Forexample, in surgery, the temperature of a patient may be controlled by abypass machine where a significant amount of the patient's blood isremoved, heated or cooled outside the body in a by-pass machine, andreintroduced to the patient's blood stream. One particular applicationof this procedure is whole body hypothermia sometimes induced duringheart surgery. Other examples include hypothermia induced duringneurosurgery or aortic or other vascular surgery.

The use of an external method for inducing hypothermia, such as a bypassmachine, is an extremely invasive procedure that subjects vastquantities of the patients' blood to pumping for an extended length oftime. External pumping of blood may be harmful to the blood, andcontinued pumping of blood into a patient for extensive periods of time,for example, more than one or two hours, is generally avoided.Additionally, such a procedure may require systemic treatment of thepatient, for example, with heparin to prevent clotting which may presentother undesirable consequences in a stroke victim.

Means of imparting heat to the blood of a patient, or removing heat fromthe patient, which do not require external pumping have been proposed.For example, one particular catheter structure which has been developedto treat patients suffering from either hypothermia or hyperthermia isdescribed in U.S. Pat. No. 5,486,208, to Ginsburg, the completedisclosure of which is herein incorporated by reference. That patentissued from one of the applications from which this application claimspriority. A catheter disclosed in that patent was inserted into a bloodvessel and a portion of the catheter heated or cooled, transferring heatto the patient's blood and thereby affecting the overall bodytemperature of the patient. However, while such devices and methods mayavoid the problems associated with external pumping of blood, they donot eliminate the difficulties that arise when the entire body issubjected to hypothermia.

There have been attempts to achieve regional cerebral hypothermia, forexample by placing the head in a cooled helmet or shroud, or eveninjecting a cold solution into the head region. Attempts to achievebrain cooling by directly cooling the surface of the head have provenimpractical or ineffective because of factors such as the insulatingqualities of the skull, which make it difficult to effectively lowerbrain core temperature, and the blood flow that may fail to providesufficient heat transfer circulation to the brain itself when thesurface of the head is cooled. Patients, especially patients not undergeneral anesthesia, may also find it difficult to tolerate immersion ordirect exposure of the head to a cold solution or cooling surface.

An apparatus to facilitate transfer of heat to or from a target locationby means of internally applied heating or cooling would be advantageous.It has been known in the art to impart heat by direct contact withspecific tissue by means of a balloon catheter. For example, in U.S.Pat. No. 5,019,075 to Spears, a heated balloon was described to applyheat directly from the surface of the balloon to the wall of an arterydilated during percutaneous transluminal coronary angioplasty (PTCA) tofuse together disrupted tissue. This device, however, operated by directcontact between the vessel wall in question and a greatly heated balloonsurface.

Balloons capable of acting as ongoing heat transfer balloons by thecontinual flow of heat transfer medium through the balloon have alsobeen shown. For example, in U.S. Pat. No. 5,624,392 to Saab, aconcentric inflow and outflow lumen each terminate within the heattransfer balloon so that a continual flow of heat transfer liquid can bemaintained within the balloon for controlled heat transfer to theadjacent tissue.

U.S. Pat. No. 5,269,758 to Taheri, discloses a balloon in which heatedfluid such as heated saline solution is circulated through a balloonthat pulses. The heat from the heat transfer liquid may then be impartedto the blood as it flows past the balloon to treat hypothermia in apatient. The flow of the affected blood is not otherwise generallydirected nor is the temperature of a target region disclosed to bealtered by the heated balloon of Tahari.

The configuration of balloons to provide channels for the flow of bloodfrom the proximal side to the distal side of a balloon blocking a bloodvessel, such as a balloon used for PTCA has also been shown. Forexample, such an autoperfusion balloon angioplasty catheter is shown inU.S. Pat. No. 4,581,017 to Sahota, and the multi-lumen balloon shown inU.S. Pat. No. 5,342,301 to Saab as discussed for use in angioplastydiscloses a multi-lumen balloon catheter configured to allow blood toperfuse from the proximal side to the distal side of a balloonangioplasty catheter when the balloon is inflated to apply angioplasticpressure against the blood vessel walls and otherwise fully obstructblood passage.

It would be desirable to devise an apparatus capable of heating orcooling liquid such as blood within the body and directing that liquidafter it is heated or cooled, to a target location. It would beparticularly advantageous if a device could be devised where the liquidcould be directed to a desired location using only the patient's ownheart as a pump. It would also be particularly advantageous if a methodcould be devised for directing heated or cooled blood to a target regionof a patient's body for a sufficient length of time to affect thetemperature of that target region.

A method of treating a patient to protect tissue, and particularlyneural tissue, by inducing hypothermia is desirable. Protectingparticular target tissue by inducing hypothermia in that tissue by meansof in situ cooling of body fluid directed to that tissue would beparticularly advantageous.

It would also be desirable to provide a system to control such a deviceto perform the method of treatment in a simple and predictable manner.It would be particularly desirable if such a system could control thedevice in conjunction with feedback data from a patient to control thedevice to predictably and selectively affect the temperature of a targetregion in the patient.

SUMMARY OF THE INVENTION

The present invention provides heat exchange catheter devices whichgenerally comprise an elongate flexible catheter having a heat exchangerwhich is operative to exchange heat between blood or other body fluidwhich flows in heat exchanging proximity thereto. Also, the presentinvention provides methods for utilizing such heat exchange catheterdevices to selectively heat or cool a particular region (e.g., thebrain, a selected portion of the brain, the spinal cord, an organ, anintra-abdominal organ, the spleen, the liver, the heart, a portion ofthe heart, a lung, a kidney, a muscle, a tumor, a site where trauma hasoccurred, a site where hemorrhage has occurred, etc.) of the body of amammalian patient.

In accordance with the devices of the present invention, there isprovided a heat exchange catheter device which may generally comprise:i) an elongate catheter having a proximal end and a distal end, theentire length of said flexible catheter being defined, as the distancefrom its proximal end to its distal end; ii) at least one fluid lumenthrough which a thermal exchange fluid may be circulated, and, iii) aheat exchanger with heat exchange fins located at a first location onthe catheter, and a working lumen extending from outside the patientthrough at least part of the catheter that is inserted into the patient.The heat exchanger is operative to exchange heat between blood whichflows in heat exchanging proximity to the heat exchanger and a thermalexchange fluid which is circulated through the catheter. The “firstlocation” at which the heat exchanger is located may constitute lessthan the entire length of the catheter, and is typically at or near thedistal end of the catheter. The heat exchanger may specifically comprisea balloon or other structure through which the thermal exchange fluidmay circulate, and the heat exchange fins may be a plurality of lobes ofthe balloon or may be surface area increasing projections (e.g.,outwardly extending protuberances, ribs, etc.) to enhance the efficiencywith which heat exchange occurs. Also, in some embodiments of thecatheter device, a body fluid channeling sleeve may be formed about theportion of the catheter whereupon the heat exchanger is located (and mayextend some distance proximal to the heat exchanger) to channel a flowof blood or other body fluid in heat exchanging proximity to the heatexchanger. Such body fluid channeling sleeve may thus be utilized tochannel available body fluid (e.g., blood) form one anatomical conduit(e.g., the descending aorta) in which the proximal end of the sleeve islocated, into a second anatomical conduit (e.g., a carotid artery) inwhich the distal end of the sleeve is located. The sleeve may be sizedand configured to form a shoulder that forms a snug seal between theoutside of the sleeve and the second anatomical conduit.

The catheter device may further be provided in combination with a device(such as a guide wire, or embolectomy catheter) or medicament (such as athrombolytic agent or barbiturate) for insertion through the workinglumen.

The catheter device of the invention may also comprise a curved heatexchange balloon with an insulated side and a thermoconductive side, andmay be placed in the anatomy such that blood flowing to the brain flowspast the thermoconductive side and blood flowing to the rest of the bodyflows past the insulated side.

Finally, another aspect of the invention is the catheter device incombination with a control system that senses body conditions such astemperature and controls the catheter in response to the body conditionssensed, such as turning off the heat exchanger when the patient's targetregion reaches a pre-selected temperature, or reactivating the heatexchanger when the temperature strays from that pre-selectedtemperature.

In accordance with the methods of the present invention, there isprovided a procedure for modulating or changing the temperature of aselected region of the body of a mammalian patient. Such methodcomprises the steps of:

a. inserting a catheter device of the foregoing character into ananatomical conduit of the patient's body through which a body fluidflows to the selected region of the patient's body, and positioning thecatheter such that body fluid flowing through the anatomical conduit tothe selected region will pass in heat exchanging proximity to the heatexchanger before reaching said selected region; and,

b. utilizing the heat exchanger of the catheter device to change thetemperature of body fluid which passes in heat exchanging proximity tothe heat exchanger, such that said body fluid will subsequently changethe temperature of said selected region of the patient's body.

Still further in accordance with the methods of the present invention,the catheter device may be positioned in a blood vessel which leads tothe brain (e.g., the right common carotid artery, left common carotidartery, innominate artery, right internal carotid artery, left internalcarotid artery, etc.) and used to cool the brain ora portion thereof todeter neural damage following a stroke or other insult (e.g., period ofischemia, period of hypoxia, hemorrhage, trauma, etc.).

Still further in accordance with the methods of the present invention,two or more catheter devices of the foregoing character may besimultaneously positioned at different sites within the patient's bodyso as to selectively heat or cool body fluid (e.g., blood) which isflowing to the selected body region, and to subsequently return suchbody fluid to or close to its original temperature as it flows from theselected body region. In this regard, one heat exchange catheter devicemay be positioned in an artery which perfuses the brain to cause coolingof the brain following a stroke or other insult, and a second cathetermay be positioned in the inferior vena cava or other suitable vein tore-warm blood after it circulates through the brain, or to generally addheat to blood going to the trunk of a patient's body to maintainnormothermia in the body at locations other than the cooled region.

Another aspect of the invention provides a method of controlling theheat exchange with the body fluid such that a predetermined temperaturemay be established at a target tissue, and may be maintained. As anadditional aspect, a predetermined temperature may be established forthe target tissue, for example a particular hypothermic temperature forthe brain, and another temperature may be selected for another region,for example the core body temperature being normothermic, and twocatheters may be simultaneously controlled to maintain both pre-selectedtemperatures.

Further aspects and details of the present invention will becomeapparent to those of skill in the relevant art upon reading andunderstanding of the detailed description of preferred embodiments setforth here below. Each of the embodiments disclosed below may beconsidered individually or in combination with any of the othervariations and aspects of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a catheter according to the present invention insertedpercutaneously into a blood vessel of a patient.

FIG. 2 depicts a catheter in which a heated or cooled fluid flowsthrough a balloon, which provides for an increased surface area near thedistal end of the catheter.

FIG. 3 depicts a catheter having a resistance heating element at itsdistal end and a balloon having longitudinal ribs to further increasethe heat transfer surface area.

FIG. 4A depicts a catheter having longitudinal fins at the distal end ofthe catheter body.

FIG. 4B depicts a catheter having radial ribs at the distal end of thecatheter body.

FIG. 4C depicts a catheter having a spiral fin to increase the heattransfer area at the distal end of the catheter.

FIG. 5 is a flow chart describing the control scheme of the invention.

FIG. 6 is a diagrammatic representation of the temperature of targettissue under the influence of the control system of FIG. 5.

FIG. 7 illustrates a preferred catheter for the selective heating andcooling of patient blood flow employing a wire coil resistance heaterand a metal foil cooling element.

FIG. 8 depicts a distal end of a catheter according to the presentinvention which is inserted into a vessel of a patient.

FIG. 8A is a cross-sectional side view of a catheter shown in FIG. 8taken along lines A-A and depicting a temperature altering region.

FIG. 9 is a side view of an exemplary catheter for heating or cooling afluid passing through an internal lumen according to the invention.

FIG. 10 is a more detailed view of a distal end of a catheter similarlyshown in FIG. 9.

FIG. 11 is a side view of an alternative catheter for heating a fluidpassing through an internal lumen according to the invention.

FIG. 11A is a side view of the catheter of FIG. 11 taken along linesA-A.

FIG. 12 is a side view of another alternative embodiment of a catheterfor heating or cooling a fluid passing through an internal lumen andhaving a plurality of perfusion orifices for allowing body fluids toenter into the internal lumen according to the invention.

FIG. 13 is a cutaway side view of a portion of a catheter similarlyillustrated in FIG. 12 showing a plurality of flaps which are closed toprevent body fluids from entering into the internal lumen when a liquidis externally injected into the lumen.

FIG. 14 illustrates a catheter similarly illustrated in FIG. 13 showingthe flaps opening to allow body fluids to enter into the internal lumenwhen no fluids are externally injected into the lumen.

FIG. 15 is a perspective view of a heat transfer catheter systemconnected to a patient that may include monitoring devices, acontroller, and a thermal catheter with multiple heat transfer portions.

FIG. 16 is a simplified perspective view of a heat transfer cathetersystem with a controller, disposable components, reusable components, aheat exchange balloon catheter and various sensors.

FIG. 17A is a simplified perspective view of a variation of the heattransfer catheter of the invention in place within the left commoncarotid artery.

FIG. 17B is a simplified perspective view of the distal portion of afinned thermal balloon catheter in accordance with one aspect of theinvention having a balloon heat transfer portion for supporting thecirculation of heat transfer fluid.

FIG. 17C is a simplified cross-sectional view of the catheterillustrated in FIG. 17B taken along line C-C.

FIG. 17D is a simplified cross-sectional view of the catheterillustrated in FIG. 17B taken along line D-D.

FIG. 17E is a simplified cross-sectional view of the catheterillustrated in FIG. 17B taken along line E-E.

FIG. 18A is a simplified perspective view of a variation of the heattransfer catheter of the invention in place within the aorta, theinnominate artery, and the right common carotid artery.

FIG. 18B is a perspective view in greater detail of the heat transfercatheter of FIG. 18A formed with a blood channeling sleeve defined byopenings that may be in communication with a fluid-containing bodyregion.

FIG. 18C is a simplified cross-sectional view of the catheterillustrated in FIG. 18B taken along line C-C.

FIG. 18D is a simplified cross-sectional view of the catheterillustrated in FIG. 18B taken along line D-D.

FIG. 18E is a simplified cross-sectional view of the catheterillustrated in FIG. 18B taken along line E-E.

FIG. 18F is a simplified cross-sectional view of the catheterillustrated in FIG. 18B taken along line F-F.

FIG. 18G is a simplified cross-sectional view of the catheterillustrated in FIG. 18B taken along line G-G.

FIG. 19 is a simplified illustration of a heat transfer catheter shownin the aorta and having a blood channeling sleeve with a proximalopening in the descending aorta and a distal opening in the left commoncarotid artery.

FIG. 20 is a simplified perspective view of a variation of the heattransfer catheter of the invention formed with an elongated shaft and atapered catheter body with spiral shaped fins, and located in the aortaand left common carotid artery.

FIG. 21A is a simplified perspective view of another variation of thethermal catheter formed with an occlusive shoulder and valve assembly.

FIG. 21B illustrates a proximal or distal sleeve valve in a closedposition for a thermal catheter of the type shown in FIG. 21A.

FIG. 21C illustrates a proximal or distal sleeve valve in an openposition for a thermal catheter of the type shown in FIG. 21A.

FIG. 21D provides a graphical representation of a heartbeat cycle withaortic blood flow measured against the synchronous opening and closingof a sleeve valve similarly shown in FIGS. 21A-C.

FIG. 22 is a heat transfer catheter with a plurality of heat transferregions that may be configured for placement in the aortic region.

FIG. 23A is a simplified perspective drawing of a version of the heatexchange catheter of the invention having an entry for cooled blood intoa central lumen, the distal end of the central lumen inserted into thecoronary ostium.

FIG. 23B is a cross-sectional view of FIG. 29 taken along lines B-B.

FIG. 24A is a simplified perspective view of a finned thermal ballooncatheter, the fins being inflatable balloon lobes.

FIG. 24B is a simplified cross-sectional view taken along the line B-Bin FIG. 24A.

FIG. 24C is a simplified cross-sectional view taken along the line C-Cin FIG. 24A.

FIG. 24D is a simplified cross-sectional view taken along the line D-Din FIG. 24A.

FIG. 24E is a simplified cross-sectional view taken along the line E-Ein FIG. 24A.

FIG. 24F is a simplified cross-sectional view taken along the line F-Fin FIG. 24A.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods and apparatus for selectivelycontrolling regional and whole body temperature by warming or cooling abody fluid such as blood in situ and directing the warmed or cooled bodyfluid to a desired location. According to the present invention, acatheter having a heat exchanger which may be, for example, a balloonwith fins, is inserted into a fluid containing portion of the patientsbody, for example, a blood vessel. A blood channeling sleeve is mountedover the heat exchanger and is open at both its proximal end (closest tothe insertion point) and its distal end (farthest along the catheterfrom the insertion point). The distal end of the sleeve is placed sothat fluid such as blood that enters the proximal end of the sleeveflows in heat transfer proximity past the heat exchanger. Heat exchangeproximity requires sufficient proximity for effective heat exchange tooccur and depends on such factors as the chemical and physical make-upof the blood, the rate of flow past the heat exchange surface, thepattern of blood flow past the heat exchanger, (laminar flow, turbulentflow, and the like), the difference in temperature between the heatexchange surface and the blood, the material of which the heat exchangesurface is made, and the proximity between the heat exchange surface andthe blood. Fluid exits the distal end of the sleeve so that the heatedor cooled blood is discharged in a desired location, for exampleupstream of target tissue such as the brain. By continuing to heat orcool fluid flowing to the target tissue for a sufficient length of time,the temperature of the target tissue is altered.

Likewise, when inducing hypothermia or hyperthermia, the inventionprovides for heating or cooling the target tissue to the desiredtemperature and maintaining that temperature by controlling the heatexchange catheter. Similarly, different regions may be controllablymaintained at temperatures different from each other by controllingdifferent heat exchange catheters at different locations with thepatient's body. Additionally, the temperature of the target tissue maybe maintained at a desired temperature, for example, mildly hypothermic,while the core temperature of the body may be monitored and maintainedat a different temperature, for example, normothermic (371 C) or nearlynormothermic, by use of a separate heat exchange catheter or anadditional heat exchange region located on the same heat exchangecatheter.

FIG. 1 depicts a distal portion 15 of a heat exchange catheter 10. Thecatheter may be inserted through the patient's skin into a blood vesselBV. Blood flow through the vessel is indicated in FIG. 1 by a set offlow arrows F. The catheter may be inserted into a relatively largeblood vessel, e.g., a femoral artery or vein, a jugular vein, sincethese vessels provide numerous advantages in that they are readilyaccessible, provide safe and convenient insertion sites, and haverelatively large volumes of blood flowing through them. In general,large blood flow rates facilitate quicker heat transfer into or out ofthe patient. For example, the jugular vein may have a diameter of about22 French, or a bit more than 7 millimeters (1 French=1 mm/π). Acatheter suitable for insertion into a vessel of this size can be madequite large relative to catheters intended for insertion into otherregions of the vascular system. Atherectomy or balloon angioplastycatheters are sometimes used to clear blockages from the coronary arteryand similar vessels. These catheters commonly have external diameters inthe range between 2 and 8 French. However, a catheter formed inaccordance with this aspect of the invention may have an externaldiameter of about 10 French or more, although this dimension mayobviously be varied a great deal without departing from the basicprinciples of the invention.

The catheter may be small enough so that the puncture site can beentered using the percutaneous Seldinger technique, a technique wellknown to medical practitioners. To avoid vessel trauma, the catheterwill usually be less than 12 French in diameter upon insertion. Once inthe vessel however, the distal or working end of the catheter can beexpanded to any size so long as blood flow is not unduly impeded.Additionally, the femoral artery and vein and the jugular vein arerelatively long and straight blood vessels. This will allow for theconvenient insertion of a catheter having a temperature controlledregion of considerable length. This is of course advantageous in thatmore heat may be transferred at a given temperature for a catheter of agiven diameter if the length of the heat transfer region is increased.Techniques for inserting catheters into the above mentioned bloodvessels are well known among medical personnel. Although the method ofthe present invention will probably be most commonly employed in ahospital, the procedure need not be performed in an operating room. Theapparatus and procedure are so simple that the catheter may be insertedand treatment may begin in some cases even in an ambulance or in thefield.

FIG. 2 depicts still another means for transferring heat to or from thedistal end of a catheter. In this embodiment, catheter shaft 20 has twolumens running through it. Fluid flows from the proximal end of thecatheter through in-flow lumen 60, through a heat transfer region 62,and back out through out-flow lumen 64. By supplying either warmed orcooled fluid through inflow lumen 60, heat may be transferred either toor from the patient's blood stream which flows in heat transferproximity to the heat transfer region. The heat transfer region 62 maybe in the form of a balloon 70. Use of a balloon may be advantageous insome embodiments to provide an increased surface area through which heattransfer may take place. Balloon inflation is maintained by a pressuredifference in the fluid as it flows through in-flow lumen 60 andout-flow lumen 64. The balloon should be inflated to a diameter somewhatless than that of the inside diameter of the blood vessel so as not tounduly impede the flow of blood through the vessel.

FIG. 3 depicts a catheter having an internal resistance heating element28 and a balloon 70, which is shown inflated. The balloon surface may beprovided with structures that increase the surface area available forheat transfer, i.e. fins. In this embodiment, the increased surface areaprovided by the inflated balloon is augmented by the presence of a setof longitudinal fins 75 on the surface of the balloon. As shown in FIGS.3 and 4A-C, longitudinal fins 75, radial ribs 77, or one or more spiralfins 79 may be disposed directly on the body 20 of a catheter.Longitudinal ribs may be advantageous because they tend to restrictblood flow through the vessel less than other configurations. In fact,these ribs insure that the balloon will not substantially block the flowof blood through the vessel because a flow path may be maintainedbetween the ribs even when the balloon is inflated. Inclusion of aballoon on a catheter employing resistance heating allows for designs inwhich current is conducted through the fluid which fills the balloon.

A catheter according to the present invention may be designed andconfigured to optimize the rate of heat transfer between the catheterand blood flowing through the vessel. While a large surface area isdesirable in order to maximize heat transfer, the catheter should beappropriately configured and sized to minimize restriction to flowthrough a blood vessel. Furthermore, the temperature of the cathetershould be carefully controlled to prevent undesirable chemical changeswithin the blood. This is especially important when applying heat to theblood as blood is readily denatured by even moderately hightemperatures. The exterior temperature of a catheter for warming bloodshould generally not exceed about 42° C.-43° C. It is estimated that acatheter whose surface temperature is controlled between 37° C. and 42°C. will provide a body core warming rate of approximately one to twodegrees Celsius per hour in a patient starting out with severehypothermia. This estimate is highly dependent on a number of factorsincluding the rate of blood flow through the vessel, the initial bodytemperature of the patient, the external surface area of the catheterthrough which heat is conducted, etc. The actual rate achieved may varysubstantially from the above estimate. The above estimate provides astarting point for a rough estimate as to the level of power transferredfrom the catheter to the patient's body and therefore of the size of thepower supply required by the system. Regardless of the exact means ofpower transmission chosen, resistance heating coil, laser and diffusingtip, direct conduction or fluid circulation, an appropriate power supplywill be required to provide heat to or remove heat from the system.

The sum of heat entering and leaving a patient's body can be written as:ΔH=H _(c) +H _(i) −H _(e)where ΔH is the sum of all heat transferred, H_(c) is the heattransferred from the catheter to the patient, H_(i) the heat produced bythe patient internally, and H_(e) the heat lost from the patient to theenvironment. If one assumes, as will ordinarily be the case in a healthypatient, that the body's internal thermoregulatory system will producejust enough heat to offset heat lost to the environment, then theequation is made simple:ΔH=H _(c).

The above equation can be written in terms of the change in thepatient's internal body temperature over time as follows:mc(ΔT/Δt)=(ΔH _(c) /Δt)where m is the body mass of the patient, c is the specific heat of thepatient's body, (ΔT/Δt) is the time rate of change of the patient'sinternal body temperature, (ΔH_(c)/Δt) is the time rate of heat deliveryfrom the catheter to the patient. If one assumes a patient having a bodymass of 75 kilograms and a specific heat of 4186 joules/° C.-kg (assumesthe specific heat of the human body to be the same as that of water, theactual value will be somewhat different), then a warming rate of 1° C.per hour (3600 seconds) will require the catheter to transfer heat tothe patient at a rate of about 87 watts (1 watt=1 joule/sec). However,as an estimate of the desirable size of a power supply to be used with acatheter of the present invention, this estimation may be too low. Thismay be true for a number of reasons. First, it was assumed for the sakeof convenience that the patient's internal system would produce anamount of heat equal to that lost to the environment. In a hypothermicpatient this will obviously not be the case. Almost by definition,accidental hypothermia occurs when a person's ability to produce heatinternally is overwhelmed by heat lost to the environment. The catheterwill have to make up the difference so the power level required willneed to be greater for that reason alone. Alternatively, to inducehypothermia, sufficient heat will need to be removed from the blood tolower the temperature of the target tissue, or in the case of whole bodyhypothermia, to remove more heat than is generated by the body. Inremoval of heat, the power required to cool the heat exchanger will belargely dependent on the efficiency of the cooling device including thedissipation of excess heat from the device to the environment.

The above estimate does not allow for power losses between the powersupply and whatever warming means is utilized. Such losses could includeresistance losses in electrical transmission lines between the powersupply and a resistance heating element, inherent inefficiencies andother losses in a system having a laser and a diffusing tip, heat lossesalong a thermally conductive shaft or fluid circulation lumen, and thelike. Any such losses which do occur will need to be compensated for byadditional power supply capacity. Furthermore, it would be undesirableto limit the performance of a catheter according to the presentinvention by limiting the size of the power supply used. It would bepreferable instead to use a power supply capable of providing powerconsiderably in excess of that actually needed and then controlling thedelivery of that power according to the measured temperature of thecatheter itself. As mentioned previously, this can be readilyaccomplished by including a sensitive temperature sensor within the bodyof the catheter. Nevertheless, the above calculation can be used as auseful estimate of the likely lower bound for sizing a power supply foruse in a catheter according to the present invention.

An alternative estimate can be made by comparing the likely performanceof the various embodiments described herein with the power requirementsfor the external blood warming apparatus presently known. Such externalwarming apparatus generally requires a supply of power on the order of1000-1500 watts and sometimes more. A device formed in accordance withthe present invention may require considerably less power than that.First, the present invention may not require an external pump tocirculate the blood; this function is provided by the patient's ownheart. Accordingly, no power is needed to drive such a pump. Secondly,the present invention may be considerably less complicated than externalblood warming systems. Known systems circulate the blood over arelatively lengthy path from the patient, through the warming element,and back into the patient. More heat may be lost over this lengthy paththan in devices described herein. Thus, the power required by externalblood circulation and warming systems of the type previously known canbe used as a rough estimate of the likely upper limit for power requiredby a system according to the present invention. It is most likely thatsuch a system may be equipped with a power supply having a capacitysomewhere between the two rough estimates described above. It istherefore contemplated that a suitable power supply will be capable ofproviding peak power somewhere in the range between 100 and 1500 watts,probably being in the range between 300 and 1000 watts. The rangesspecified are an estimate of suitable peak power capability. The powersupply will most commonly be thermostatically controlled in response toa temperature sensor in the body of the catheter. The actual effectivepower transmitted to the patient will therefore typically be much lessthan the peak power capacity of the system power supply.

The above calculations refer primarily to a system for heating theblood. With respect to a catheter for cooling the blood, the temperatureand power constraints may not be as limiting. Care should be taken toavoid freezing the blood or inducing shock to the patient fromexcessively rapid cooling. The primary component of blood is essentiallywater with a number of suspended and dissolved substances. As such, itsfreezing point is somewhat below 0° C. However, a catheter adapted tocool blood in a hyperthermic patient or to induce an artificialhypothermia will usually not be operated at temperatures that low. It ispresently contemplated that the external surface of such a catheter maybe held in the range between about 1° C. and 20° C., although the actualtemperature could vary between about 0° C. and the patient's currentbody temperature. Additionally, for example, of the case of a heatexchange balloon of some length, the surface temperature of the balloonmay vary along its length as it gives off heat to the blood. A balloonmay vary in temperature as much as 12° C. or more along its length.

Another aspect of the present invention further provides methods forboth raising the body temperature of initially hypothermic patients andlowering the body temperature of patients who are initiallyhyperthermic, or for whom the body temperature is to be lowered belownormal for some other purpose. In such cases, it is generally necessaryto monitor the target tissue (which in whole body hypothermia may be thewhole body and in regional may be, for example, the brain) and controlthe cooling so the desired temperature will not be exceeded for example,by the physiologic response of the patient. In such cases, this aspectof the invention specifically provides for reversing the heat transferprocess to maintain the target tissue at the selected temperature.

As set forth in FIG. 5, a sample control scheme is provided herein foreither warming or cooling target tissue to a preferred temperature andmaintaining the tissue at about the preferred temperature. The controlscheme is described by the flow chart shown in FIG. 5 and illustratedwith the graph shown in FIG. 6. A preferred temperature is pre-selectedfor the target temperature, for example a temperature of 311° C. for thebrain tissue. This pre-selected temperature is communicated to a controlunit, for example by setting a desired temperature on a control unit fora heat exchange catheter. A heat exchange catheter capable of eitherremoving heat from the blood or adding heat to the blood is inserted sothat it is in heat exchange proximity with blood in a blood vessel thatdelivers blood to a target location such as the brain. The catheter iscontrolled by the control unit described above that may turn the heatexchanger off or on and may control the heat exchanger to heat or coolthe blood which is in heat exchange proximity with the heat exchanger.

The temperature of the brain is monitored, for example by a temperatureprobe inserted into the brain tissue or by measuring temperature at someproxy location such as the tympanic membrane or nasal cavity provides atemperature measurement that represents the brain temperature. Thisresults in a sensed temperature measurement that is communicated to thecontroller. An upper variance set point is determined, for example 2degree above the pre-selected temperature, and communicated to thecontroller. In this example, that would result in an upper variance setpoint of 3121. A lower variance set point is also determined andcommunicated to the controller, for example 2 degrees below thepre-selected temperature, resulting in this example in a lower varianceset point of 3021.

When the heat exchanger is cooling, the sensed temperature of the targettissue is compared with the pre-selected temperature. If the sensedtemperature is above the pre-selected temperature, the coolingcontinues. If the sensed temperature falls to the pre-selectedtemperature or below, then the controller acts to turn the heatexchanger off. After the heat exchanger is turned off, the temperatureof the target tissue is again measured to obtain a sensed temperature.If the sensed temperature is above the upper variance set point, thecontroller acts to cause the heat exchanger to begin cooling again. Thiscooling continues until the temperature again reaches the pre-selectedtemperature. At this point, the controller once again acts to turn theheat exchanger off. If the patient's body is generating heat in thetarget tissue at a rate greater than the loss to the environment, it maybe seen that the temperature will oscillate between the preferredtemperature and the upper variance set point, in this example, between311 C and 3121 C as illustrated by section A of FIG. 6.

In some instances, the temperature of the target tissue may continue tofall spontaneously after the heat exchanger is turned off, for exampleif the brain tissue is giving off more heat to the environment than isgenerated by the brain. In such a situation the sensed temperature maycontinue to fall until it is below the lower variance set point. If itdoes, the controller acts to cause the heat exchanger to add heat to theblood and thus to the target tissue until the sensed temperature isagain at the pre-selected temperature. The controller then turns theheat exchange catheter off. If the temperature again falls until itreaches a temperature below the lower variance set point, the process isrepeated. If this situation repeats, it may be seen that the temperaturewill oscillate between the pre-selected temperature and the lowervariance set point, in this example, between 311° C. and 321° C. asillustrated by section B of FIG. 6.

The example given here was for purposes of illustration only and manyvariations will be anticipated within the scope of this invention. Forexample, the pre-selected temperature and upper and lower variance setpoints may be different than those described above. The discussion abovewas an example of cooling the target tissue to a temperature belownormothermic. However it may be seen that a pre-selected temperatureabove normothermic may also be selected, and a heat exchanger which iscontrolled to both add heat to the blood or remove heat from the bloodmay, through use of the same control scheme, maintain the temperature ofthe target tissue at the preferred temperature within the upper andlower variance set points around a pre-selected temperature abovenormothermic. It may also be readily perceived that a patient that ishypothermic may be rewarmed to normothermia by setting the preselectedtemperature in the control scheme illustrated to 37° which will causethe heating element to warm the blood until the sensed temperaturereaches 37°. The anticipation and prevention of temperature overshootmay be accomplished as described in U.S. patent application Ser. No.08/584,013 previously incorporated herein by reference.

In the example given, the steps are all stated as discrete actions, suchas measuring the temperature of the target tissue or comparing sensedand pre-selected temperatures, but it may be readily understood by oneof skill in the art that the actions may be relatively continuous. Itwill also be readily appreciated that control criteria other than thetemperature of the target tissue may be substituted and controlled, forexample blood pressure or cranial pressure, or temperature derived fromsome other location, and two control schemes as described may besimultaneously instituted for different locations in the patient, forexample, to cool a region such as the brain and maintain that region ina relatively stable cooled condition while simultaneously warming thecore temperature of the patient to normothermic and maintaining thepatient's core temperature relatively stable at a normothermictemperature. The method of affecting the target tissue's temperaturediscussed above was cooling the blood upstream from the target tissue,but it may be appreciated that other methods of heating and cooling, forexample heating or cooling cerebrospinal fluid circulating around thebrain or spinal cord may be employed.

A system for the selective warming and cooling of patients isillustrated in FIG. 7. The system may comprise a catheter 100 having aproximal end 102, a distal end 104, a heat-generating surface 106 nearthe distal end, and a heat-absorbing surface near the distal end 108.The heat-generating surface 106 may include any of the heat transfercomponents described above, particularly a wire coil resistance heateras shown having from 50 to 1000 windings, typically spaced-apart from0.1 mm to 1 mm. The total length of the catheter may range from 15 cm to50 cm, and may measure from about 1 mm to 5 mm in diameter. The windingsmay extend over a total distance in the range from 10 cm to 20 cm nearthe distal end. The heat-absorbing surface may be a thermally conductivemetal foil, typically composed of a biologically compatible thermallyconductive metal, such as gold, silver, aluminum, or the like. Coppermay also be useful, but should be treated or encapsulated in order toenhance its biocompatibility. The metal foil may be thin in order toenhance flexibility of the catheter body, typically having a thicknessin the range from 0.001 mm to 0.01 mm. The heat-absorbing surface 108may be conductively coupled to a cooler located externally of thecatheter, typically in a control unit 120 as described below. In theillustrated embodiment, the surface 108 is coupled by a thermallyconductive core member 110 composed of a flexible rod or wire formedfrom one of the thermally conductive metals described above.Alternatively, thermal coupling can be achieved by extending the surface108 proximally so that the proximal end of the surface can be coupled tothe cooler. In the latter case, it may be preferable that the proximalportions of the surface 108 be thermally insulated to prevent coolingoutside of the blood circulation. The system may further comprise acontrol unit 120 which typically provides both the heat-generator andthe cooler for coupling to the catheter 100. The heat-generator may alsocomprise a direct current source for coupling to the resistance heateron the catheter. Usually, the direct current source will be acommercially available, temperature-controlled DC power supply,typically operating at a voltage in the range from 10 VDC to 60 VDC anda current output in the range from 1 A to 2.5 A. The power supply may becontrolled to maintain the surface temperature of the heating surface106 in the range from 40° C. to 42° C. As discussed above, the surfacetemperature should not exceed 42° C. in order to prevent damage to bloodcomponents. Other desirable characteristics of the heat exchange surfaceare described above.

Alternatively, the temperature of the heat exchange surface can also becontrolled based on measured blood temperature and/or measured bodytemperature. Blood temperature can be measured by temperature sensorspresent on the catheter. For example, a temperature sensor 112 may belocated on the catheter spaced-apart from the heat exchange surfaces 106and 108. The temperature sensor 112 may be located either upstream ordownstream from the heat exchange surfaces based on the direction ofblood flow and depending on the manner in which the catheter isintroduced to the patient. Optionally, a pair of temperature sensorscould be provided, one disposed on each side of the heat exchangesurfaces in order to measure both upstream and downstream bloodtemperatures. The catheter may also include a temperature sensor (notshown) coupled directly to the heat-generating surface 106 so that thetemperature of the surface may be directly controlled. Other temperaturesensors (not shown) may be provided for directly measuring the patient'score body temperature or the temperature of various regions of thepatient's body, with the temperatures being fed back into the controlunit 120. The cooler in control unit 120 may be any type ofrefrigeration unit capable of removing heat from the heat-absorbingsurface 106 at a rate sufficient to cool the blood at a desired rate.Typically, the cooler may be rated at from 150 W to 350 W.

The cooler will be a thermoelectric cooler, such as those commerciallyavailable from Melcor Thermoelectrics, Trenton, N.J. 08648. The coolermay be directly coupled to the core element 110 so that direct heatconduction from the heat-absorbing surface 108 may be effected to thecooler in control unit 120. The temperature of the cooling surface 108may be less critical than that of the heating surface 106 with regard tothis aspect of the invention, but will usually be maintained in therange from 0° C. to 35° C. preferably being below 30° C. The temperatureof the cooling surface may be directly controlled within this range, oralternatively, the system may be designed so that the coolingtemperature operates approximately within this range based on the totalsystem characteristics.

The control unit 120 may further include one or more temperaturecontrollers for controlling the temperature of the heat-generatingsurface 106 and the heat-absorbing surface 106 based on the bloodtemperature and/or the body temperature. At a minimum, the control unit120 may control the temperature of the heat-generating surface 106within the range set forth above, and may monitor at least one of thepatient blood temperature and patient body temperature in order toreverse the heating or cooling mode as discussed above. With respect tothe control scheme described in FIG. 10, for example, the system mayoperate in an on-off mode where for example hypothermic patients areinitially treated by warming the blood at a constant surface temperaturerate until a target temperature is reached. When the target temperatureis reached, power to the heat-generating surface 106 is turned off.Monitoring of the blood and/or patient body temperature, however, ismaintained to assure that the patient temperature does not exceed amaximum which is above the target temperature. Should the maximum beexceeded, then the system is operated in the cooling mode until theexcess body temperature is lowered. Usually, there will be no need toagain warm the patient, but the present system may provide for furthercycles of warming and cooling if necessary. For initially hyperthermicpatients, the cooling and warming modes are reversed. It will beappreciated that the temperature control schemes of the presentinvention could be substantially more sophisticated. For example, thepower input to warm the patient could be controlled based onproportional, derivative, or integral control schemes which willtypically provide for a tapering of the heat transfer rate as thepatient's core or regional body temperature approaches the desiredtarget level. Moreover, cascade control schemes based on both patientblood temperature and patient body temperature could be devised. Suchcontrol schemes, for example, could be adapted both for warming thepatient and cooling the patient with mathematical models of typicalpatient physiological characteristics being taken into account inpreparing the control schemes. However, a simple off-on control schemethat is capable of reversing the heat transfer mode if the targettemperature is exceeded by more than a safe amount will be sufficient.

Another aspect of the invention provides methods and apparatus forregulating the temperature of a fluid that is to be delivered to atarget location within a patient while the fluid is within the body. Theregulation of the fluid temperature in this manner lends itself to avariety of applications including heating or cooling the temperature ofdrugs, solutes, or blood before their delivery to a target site.Regulation of the temperature of the injected fluid may also find use inregulating the temperature of the target location itself in preparationfor various medical procedures, including neurosurgical procedureswithin the brain. Further, the methods and apparatus allow for thetemperature of tissue within a patient's body temperature to becontrolled by warming or cooling the patient's blood in situ. By warmingor cooling the patient's blood that subsequently flows to that tissue,the temperature of the tissue in question may thereby be increased ordecreased as desired. Such methods and apparatus therefore provide aconvenient therapy for treating hypothermia or hyperthermia, or forinducing regional cooling or heating.

FIG. 8 depicts a distal end 210 of a catheter 212 formed in accordancewith another aspect of the present invention. The catheter 212 may bepositioned within a blood vessel BV. Blood flow through the vessel isindicated in FIG. 8 by a set of arrows F. The distal end 210 of thecatheter 212 may include a temperature altering region 214 although itwill be appreciated that the temperature altering region may be locatedanywhere between the proximal and the distal catheter end. Techniquesfor inserting catheters into various blood vessels such as the Seldingertechnique mentioned above, are well known among medical personnel. Thecatheter 212 may be manufactured in various sizes depending upon theparticular application. For most uses, it may have a length in the rangefrom about 30 cm to about 130 cm, and a diameter in the range from 6 to12 French (1 French=0.33 mm). The catheter 212 will preferably beflexible to allow the catheter to be moved through various vesselswithin a patient, and may be positioned in the body preferably with theassistance of a guidewire.

As shown in FIG. 9, the catheter 212 may include an internal lumen 216.A temperature altering mechanism 218 may be provided adjacent theluminal wall of the lumen 216 at the temperature altering region 214.For convenience of discussion, the temperature altering mechanism 218 isillustrated schematically and may comprise a variety of mechanisms thatare employed to either heat or cool the luminal wall of the lumen 216 toheat or cool the fluid passing through the lumen 216 at the temperaturealtering region 214. Exemplary mechanisms for heating or cooling theluminal wall may include heated or cooled fluids passing through thecatheter 212 near the luminal wall, resistive elements disposed withinthe catheter 212, laser energy that is supplied to the temperaturealtering region, various chemicals disposed within the catheter body,thermoelectric crystal, and the like.

Use of such mechanisms allow fluids passing through the lumen 216 at thetemperature altering region 214 to have their temperature altered sothat they will be within a desired range when exiting the catheter 212.The temperature altering mechanism 218 may be configured to heat a fluidpassing through the temperature altering region so that its temperaturewill be heated by at least 5° C. to about 42° C.

When cooling a fluid, the temperature altering mechanism 218 may beconfigured to cool the fluid by at least 7° C. to about 30° C. Thetemperature altering mechanism 218 may be designed to optimize the rateof heat transfer between the catheter and a fluid flowing through theinternal lumen. Further, the temperature of the catheter may becarefully controlled to prevent undesirable chemical changes within theblood. This is especially important when applying heat to the blood asblood is readily denatured by even moderately high temperatures. Thetemperature of the luminal wall for warming blood should generally notexceed about 42° C. to 43° C. The amount of energy that may be suppliedto heat a patient's core body temperature is described in U.S. Pat. No.5,486,208, previously incorporated by reference herein. The temperaturealtering mechanism 218 may be also arranged within the catheter 212 sothat the temperature of the luminal wall may be heated or cooled withoutsubstantial direct heating of an outer surface of the catheter. In thisway, the catheter 212 may be employed to selectively heat or cool aspecific target site by simply positioning the distal end of thecatheter at the target site and introducing a fluid through the lumen216.

As shown in FIGS. 9 and 10, a catheter 220 formed in accordance withthis aspect of the invention may circulate a heat transfer fluid toalter the temperature of a fluid passing through the catheter. Thecatheter 220 comprises a catheter body 222 having a proximal end 224 anda distal end 226. A lumen 228 extends between the proximal end 224 andthe distal end 226. At the proximal end 224, is a proximal port 230through which various fluids may be introduced into the lumen 228 fromoutside of a patient. Passing through the catheter body 222 is a firstfluid path 232 and a second fluid path 234 as particularly shown in FIG.10. A first port 236 is in communication with the first fluid path 232and a second port 238 is in communication with the second fluid path234. In this manner, a heated or cooled heat transfer fluid may beintroduced into the first port 236 where it passes through the firstfluid path 232 adjacent to the lumen 228. As the heat transfer fluidpasses through the first fluid path 232, heat is transferred either toor from a fluid passing through the lumen 228 to heat or cool the fluidto a desired temperature before exiting the catheter body 222. Afterpassing through the first fluid path 232, the heat transfer fluidcirculates back through catheter body 222 through the second fluid path234 where it exits the second port 238.

FIGS. 11 and 11A provide illustrations of yet another variation of theinvention that includes a catheter 240 with resistive heating to heat afluid passing through the catheter. The catheter 240 comprises acatheter body 242 having a proximal end 244 and a distal end 246. Alumen 248 passes through the catheter body 242 between its proximal end244 and distal end 246. A proximal port 250 is provided to facilitatethe introduction of fluids into the lumen 248 from outside a patient.Disposed within the catheter body 242 near the lumen 248 are a pluralityof wires 252 as shown in FIG. 17. These wires 252 may exit the catheterbody 242 through a port 254. The wires 252 may be also connected toeither a DC or low frequency AC power supply. As electrical currentpasses through the wires 252, some of the energy is dissipated as heatto heat the luminal wall. Alternatively, a radio frequency or RF powersupply may be employed to supply power to electrodes disposed within thecatheter body 242 to heat the luminal wall.

Referring now to FIGS. 12-14, a catheter 256 may be employed to heat orcool an externally injected fluid, to heat or cool a body fluid in situ,or a combination of both. The catheter 256 may comprise a catheter body258 having a proximal end 260 and a distal end 262. Extending betweenthe proximal end 260 and the distal end 262 is a lumen 264 as shown inFIG. 12. A proximal port 266 is also provided at the proximal end 260 toallow various fluids to be injected into the lumen 264 while port 266 ispositioned outside a patient. At the distal end 262 is a temperaturealtering region 268 which includes a temperature altering mechanism (notshown). The particular temperature altering mechanism may comprise anyof those described with respect to other aspects of the invention setforth above or hereafter. In this manner, a fluid which is injected intothe port 266 will pass through the lumen 264 and have its temperaturealtered when passing through the temperature altering region 268 in amanner similar to that previously described with other embodiments. Thecatheter body 258 may include a plurality of perfusion orifices 270which extend through the wall of the catheter body to provide fluidpaths to the lumen 264. As shown by the arrows in FIG. 12, a body fluid,such as blood, may pass through the orifices 270 and into the lumen 264where it will have its temperature altered at the temperature alteringregion 268 so that the temperature of the body fluid will be within adesired range when exiting the catheter body 258 at its distal end 262as shown.

As illustrated in FIGS. 13 and 14, the luminal wall of the catheter body258 may include a plurality of flaps 272. These flaps 272 may controlthe passage of body fluids through the orifices 270 and into the lumen264. These flaps 272 or similar structures may be also constructed asdescribed in U.S. Pat. No. 5,180,364, the disclosure of which is hereinincorporated by reference. When a fluid is injected into the lumen 264at the port 266, the pressure and direction of flow of the injectedfluid will cause the flaps 272 to close over the orifices 270 as shownin FIG. 13 so that essentially only the injected fluid will pass throughthe temperature altering region 268. In this way, the temperature of theinjected fluid will have its temperature altered so that it will bewithin a desired range when exiting the distal end. As shown in FIG. 14,when no fluids are injected into the port 266, the pressure of the bodyfluid within a vessel will cause the flaps 272 to open to allow the bodyfluids to flow through the orifices 270 and into the lumen 264. In thismanner, a body fluid, such as blood, may have its temperature altered bypassing through the orifices 270 and through the temperature alteringregion 268. The configuration of the flaps 272 is particularlyadvantageous in applications where the temperature of a patient's tissueis altered. By simply introducing the catheter 256 into the patient, theblood which flows into the lumen 264 via the orifices 270 will have itstemperature altered by the time it exits the distal end 262.

This may result in whole body temperature alteration, or if the blood isdirected to a specific site by the catheter, may result in regionaltemperature alteration. In the event that a solute or drug is alsoneeded for therapy, it may be introduced into the lumen 264 through theport 266 and have its temperature be substantially the same as theexiting blood temperature. As described above, this aspect of theinvention provides methods and apparatus which are useful in regulatingthe temperature of various fluids while such fluids are within apatient. With such an arrangement, a variety of procedures may beperformed including the introduction of a drug or solute from outsidethe patient that may have its temperature altered within the catheterbefore reaching a target location. Furthermore, a fluid may be heated orcooled within the catheter to in turn heat or cool a specific region ofa body structure prior to the performance of a medical procedure. Inanother alternative, the temperature of a patient's body fluid, such asblood, may be altered in situ to treat a patient suffering from eitherhypothermia or hyperthermia, or to intentionally induce either wholebody or regional hypothermia.

Another aspect of the present invention provides methods and apparatusfor regional and whole body temperature modification. The lowering ofbody temperature for selected regions may provide a neuroprotectiveeffect particularly in proximity to the brain. Selected portions of atleast one catheter may, for example, cool fluids such as blood orcerebral spinal fluid that are in contact with, circulating in, around,or leading to the brain region. The cooled body fluid may be selectivelydirected to a chosen region of the patient's body for producing aregionally confined cooling effect. Alternatively, a patient's wholebody temperature may be reduced to provide, for example, neuroprotectionfor the entire brain and other widely spaced tissue such as the spinalcord. As will be discussed in further detail below, methods andapparatus provided herein may include a heat exchange catheter formedwith an increased surface area or a finned section to provide rapid andeffective heat transfer. A regionally confined thermal transfer regionalong a catheter body having a longitudinal dimension may furtherprovide effective heat transfer with fluids traveling within an innerpassageway, while the catheter may further provide a zone of regionalcooling or heat transfer along selected portions of the catheter.Various combinations of both heating and cooling elements may be definedalong different portions of a single catheter, or as part of a series orcombination of heat exchange devices as similarly described with respectto other aspects of the invention. All of these devices and proceduresmay be directed to regional or selected body temperature modificationthat is particularly suitable for the cooling of the cerebral region,and for inducing an artificial state of hypothermia that may providetherapeutic benefits in the treatment of cerebrovascular injury. Thesystem may be a simple heat transfer catheter with manual controls, ormay be operated by means of a controller that may monitor a number ofsensors and control the heat exchange catheter in response to datareceived form said sensors.

As generally shown in FIG. 15, a heat transfer catheter system directedto this aspect of the invention may include a catheter control unit 300and a heat transfer catheter 302 formed with a combination of at leastone heat transfer section. The heat transfer section or sections arelocated on that portion of the catheter, as illustrated by section 319,that is inserted into the patient. This insertion portion is less thanthe full length of the catheter and extends from the location on thecatheter just inside the patient, when the catheter is fully inserted,to the distal end of the catheter. The catheter control unit 300 mayinclude a fluid pump for circulating a heat exchange fluid or mediumwithin the catheter 302, and a combination of at least one heatexchanger component for heating and/or cooling circulating fluids withinthe heat transfer system. A reservoir or fluid bag 306 may be connectedto the control unit 300 to provide a source of heat transfer fluid suchas, saline, blood substitute solution or other biocompatible fluid. Thecontrol unit 300 may further receive data from a variety of sensorswhich may be, for example, solid state thermocouples to provide feedbackand patient temperature information from selected organs or portions ofthe body such as a temperature probes for the brain and head region 308,a rectal temperature probe 309, an ear temperature probe 311, a bladdertemperature probe (not shown) and the like. Based upon sensedtemperatures and conditions, the control unit 300 may direct the heatingor cooling of the catheter in response to input from the sensors. Thecontrol unit 300 may activate a heat exchanger at a first sensedtemperature, and may also deactivate the heat exchanger at a secondsensed temperature which may be relatively higher or lower than thefirst sensed temperature or any other predetermined temperature.

The control unit 300 may of course independently heat or cool selectedheat transfer sections to attain desired or preselected temperatures inbody regions. Likewise the controller may activate more than one heatexchanger to control temperature at particular regions of the patient'sbody. The controller might also activate or deactivate other apparatus,for example, external heating blankets or the like, in response tosensed temperatures. The controller may function as described above andillustrated in FIGS. 5 and 6.

The temperature regulating catheter 302 illustrated in FIG. 15 may alsoprovide various zones of cooling and/or heating by circulating heattransfer medium through a series of inlet and an outlet conduits. Afirst and a second fluid path 312 and 314 may provide a heat exchangerchannel within the catheter, and may be respectively connected to theinlet 316 and outlet 317 of a pump for circulation of a heat transferfluid to cool the flow of fluid within a selected body region. A similararrangement may be implemented for heating a selected body regionsimultaneously or independently from the cooling component of thesystem.

The catheter control unit 300 may further include a thermoelectriccooler and heater which are selectively activated and deactivated toperform both heating and cooling functions with the same or differentheat transfer medium within the closed-loop catheter system. Forexample, a first heat transfer section 318 of at least one temperatureregulating catheter 302 and located on the insertion portion 319 of thatcatheter, may circulate a cold solution in the immediate head region, oralternatively, within a carotid artery or other blood vessel leading tothe brain. The head temperature may be locally monitored withtemperature sensors 308 positioned on a relatively proximate exteriorsurface of the patient or within selected body regions. Another or asecond heat transfer section 320 of the catheter 302, also located onthe insertion portion 319, may circulate a heated solution within acollapsible balloon or otherwise provide heat to other body locationsthrough heating elements other mechanisms described in accordance withother aspects of the invention. While the heat transfer catheter 302 mayprovide regional hypothermia to the brain region for neuroprotectivebenefits, other parts of the body may be kept relatively warm so thatadverse side effects such as shivering may be avoided or minimized.Warming of the body generally below the neck may be further achieved byinsulating or wrapping the relatively lower body in a heating pad orblanket 322 while the head region 310 above the neck is cooled. Itshould be understood of course that multiple heat transfer sections ofthe catheter 302 may be modified to provide whole body cooling orwarming to affect body core temperature, and is not just limited toregional or localized body temperature regulation.

FIG. 16 provides an illustration of the heat transfer catheter system ofthe invention which includes disposable components including a heattransfer catheter 324, a disposable heat exchange plate 338, a pump headassembly 340, a saline bag 339, sensors 348, 344 and a fluid flow line337, as well as reusable components including a solid statethermoelectric heater/cooler 342, a pump driver 343 and various controlsfor the unit.

The heat transfer catheter 324 is formed with a blood channeling sleeve325, a catheter shaft 326, and a heat exchanger 327 which may be forexample a heat exchange balloon operated using closed-loop flow of heatexchange medium. The catheter shaft may be formed with a working lumen328 for injection of drugs, fluoroscopic dye, or the like, and forreceipt of a guide wire 329 for use in placing the heat transfercatheter at an appropriate location in the patient's body. The proximalend of the shaft may be connected to a multi-arm adapter 330 forproviding separate access to various channels in the catheter shaft. Forexample, one arm 336 may provide access to the central lumen 328 of thecatheter shaft for insertion of a guide wire 329 to steer the heattransfer catheter to the desired location. Where the heat exchanger 327is a heat exchange balloon for closed-loop flow of a heat exchangemedium 331, the adapter may contain an arm 332 to connect an inlet flowline 333 to an inlet flow channel (not shown in this FIG.) within thecatheter shaft, a separate arm 334 to connect an outlet fluid line 335to an outlet flow channel (also not shown in this FIG.) A dual channelflow line 337 may contain both inlet and outlet flow lines 333, 335 toconnect the catheter shaft 326 to a disposable heat exchange plate 338.Additionally, one of the flow lines, for example the inlet flow line 333may be connected to a bag 339 of heat exchange fluid 331 to prime theclosed-loop heat exchange balloon catheter system as necessary.

The heat exchange plate 338 may include a serpentine pathway 339 for theheat exchange fluid to be pumped through the heat exchange plate bymeans of a disposable pump head 340. The heat exchange plate includingthe serpentine pathway and the pump head is configured to install into areusable master control unit 341. The master control unit may include aheat generating or removing unit 342 such as a thermoelectricheater/cooler (TE cooler). A TE cooler is particularly advantageousbecause the same unit is capable of either generating heat or removingheat by changing the polarity of current activating the unit. Thereforeit may be conveniently controlled to supply or remove heat from thesystem without the need of two separate units.

The master control unit includes a pump drive 343 that activates thepump head 340 to pump the heat exchange fluid 331 and cause it tocirculate through the heat exchanger 327 and the serpentine path in theheat exchange plate. When installed, the heat exchange plate is inthermal communication with the TE cooler, and thus the TE cooler may actto heat or cool the heat exchange fluid as that fluid is circulatedthrough the serpentine pathway. When the heat exchange fluid iscirculated through the heat exchanger located in a patient's body, itmay act to add or remove heat from the body. In this way the TE coolermay act to affect the blood temperature of a patient as desired.

The TE cooler and the pump are responsive to a controller unit 344. Thecontrol unit receives data input through electrical connections 345,346, 347 to numerous sensors, for example body temperature sensors 348,349 that may sense temperatures from a patient's ear, brain region,bladder, rectum, esophagus or other appropriate location as desired bythe operator who places the sensors.

Likewise, a sensor 350 may monitor the temperature of the heat exchangeballoon, and other sensors (not shown) may be provided as desired tomonitor the blood temperature at the distal tip of the catheter, at theproximal tip of the catheter, or other desired location.

An operator by means of the manual input unit 351 may provide theoperating parameters of the control system, for example a pre-selectedtemperature for the brain. The parameters are communicated to thecontrol unit 344 by means of a connection 353 between the manual inputunit and the control unit.

In practice, the operator using the manual input unit supplies a set ofparameters to the control unit 344. For example, a desired temperaturefor the brain region and/or the whole body of the patient may bespecified as the pre-selected temperature. Data is received from thesensors 348, 349 indicating for example, a sensed temperature of thepatient at the location of the sensors, e.g. the actual core bodytemperature of the patient or the actual temperature of the brainregion. Other data input may include the actual temperature of the heatexchanger, the temperature of blood at the distal end of the catheterbody, or the like.

The control unit coordinates the data and selectively actuates thevarious units of the system to achieve and maintain parameters. Forexample, it may actuate the TE cooler to increase the amount of heat itis removing if the actual temperature is above the specifiedtemperature, or decreasing the amount of heat being removed if thetemperature is below the specified temperature. It may stop the pumpingof the heat exchange fluid when the body or regional temperature sensedis the desired temperature.

The controller may have a buffer range for operation wherein a targettemperature is established, and an upper variance set point temperatureand lower variance set point temperature are also set. In this way, thecontroller may cause the heat exchanger to operate until the targettemperature is reached. At that temperature, the controller may suspendthe operation of the heat exchanger until either the upper variance setpoint temperature is sensed or the lower variance set point temperatureis reached. When the upper variance set point temperature is sensed, thecontroller would then activate the heat exchanger to remove heat fromthe blood stream. On the other hand, if the lower variance set pointtemperature is sensed, then the controller would activate the heatexchanger to add heat to the blood stream. This control scheme issimilar to that illustrated in FIGS. 5 and 6 discussed above. Such acontrol scheme as applied to this system has the advantage of allowingthe operator to essentially dial in a desired temperature and the systemwill act to reach that target temperature and maintain the patient atthat target temperature. At the same time, a buffer range is establishedso that when the target temperature is reached, the controller willgenerally not turn the TE cooler on and off or activate and deactivatethe pump drive in rapid succession, actions that would be potentiallydamaging to the electric units in question.

It may also be perceived, in keeping with the present invention, thatthe controller may be configured to simultaneously respond to severalsensors, or to activate or deactivate various components such as severalheat exchangers. In this way, for example, a controller might heat bloodthat is subsequently circulated to the core body in response to a sensedcore body temperature that is below the target temperature, andsimultaneously activate a second heat exchanger to cool blood that isdirected to the brain region in response to a sensed brain temperaturethat is above the target temperature. It may be that the sensed bodytemperature is at the target temperature and thus the heat exchangerthat is in contact with blood circulating to the core body may be turnedoff by the controller, while at the same time the controller continuesto activate the heat exchanger to cool blood that is directed to thebrain region. Any of the many control schemes that may be anticipated byan operator and programmed into the control unit are contemplated bythis invention.

An advantage of the system as illustrated is that all the portions ofthe system that are in contact with the patient are disposable, butsubstantial and relatively expensive portions of the system arereusable. Thus the catheter, the flow path for sterile heat exchangefluid, the sterile heat exchange fluid itself, and the pump head are alldisposable. Even if a rupture in the heat exchange balloon permits theheat exchange fluid channels and thus the pump head to come in contactwith a patient's blood, no cross-contamination will occur betweenpatients because all those elements are disposable. The pump drive, theelectronic control mechanisms, the TE cooler, and the manual input unit,however, are all reusable for economy and convenience. Likewise, thesensors may be disposable, but the control unit to which they attach isreusable.

It will readily be appreciated by those of skill in the art that thesystem described here in detail may be employed using numeroussubstitutions, deletions and alternatives without deviating from thespirit of the invention as herein claimed. For example, but not by wayof limitation, the serpentine pathway may be a coil or other suitableconfiguration, the sensors may sense a wide variety of body locationsand other parameters may be provided to the control unit, such astemperature or pressure, the heat exchanger may be any appropriate type,such as a thermal electric heating unit which would not require thecirculation of heat exchange fluid. If a heat exchange balloon isprovided, a pump might be provided that is a screw pump, a gear pumpdiaphragm pump, a peristaltic roller pump, or any other suitable meansfor pumping the heat exchange fluid. All of these and othersubstitutions obvious to those of skill in the art are contemplated bythis invention.

FIGS. 17A-E provide illustrations an embodiment of a heat exchanger ofthe invention. As shown in FIG. 17A, a heat exchange balloon catheter360 with a finned balloon portion 362 may be positioned within at leasta portion of the descending aorta 364 and a blood vessel 366 conductingblood flow to the brain region. It should be understood that the balloonportion 362 may be formed of material that is sufficiently thin topromote effective thermal transfer between heat exchange fluid withinthe balloon and blood flowing within heat exchange proximity of theballoon, but not excessively elastic to expand and unintentionallyobstruct a fluid passageway or blood vessel 366. Indeed, the use ofthin, strong but relatively inelastic material such as PET is desirableto obtain a predictable balloon configuration with adequate heatexchange properties. The catheter shaft 368 of the thermal catheter 360provided herein may be placed in a desired location relative to aselected body region or artery 366 by conventional techniques such asguiding catheters or steerable wire over-the-wire technique as known tothose of ordinary skill in the field. The balloon portion 362 of thecatheter 360 may support the closed-loop circulation of a heat transferfluid as described herein. The increased surface area may provideeffective heat transfer within a body region by thermal conduction, andmay further permit blood continued blood flow without substantialdisruption by creating channels exterior of the balloon surface when theballoon is expanded.

FIG. 17B illustrates a heat exchange balloon 360 mounted on a shaft 368defined by a longitudinal axis and a plurality of heat transfer fins369, 371, 373, 375 projecting radially outward from the longitudinalaxis 370 of the catheter shaft. The heat transfer fins may be formed,for example, as the lobes of a multi-lobed, collapsible balloon. Theshaft 368 is generally round and in this embodiment includes a workinglumen 370 running through the shaft and open at the distal end of thecatheter. The working lumen may be used for the injection of medicamentswhich may include, for example, a thrombolytic agent, an anticoagulant,a neuro-protectant, a barbiturate, a anti-seizure agent, an oxygenatedperfusate, a vaso-dilator, an agent which prevents vaso-spasm, an agentto prevent platelet activation, and an agent to deter the adhesion ofplatelets. Alternatively, the working lumen may be used for theinjection of flouroscopic dye, for the receipt of a guide wire 329, oras a guiding catheter for various diagnostic or therapeutic devicesincluding, for example, an angioplasty catheter, an embolectomycatheter, an occlusion member delivering catheter, an embolizationmember delivering catheter, an electro-cautery device, or amicrocatheter. The shaft exterior of the central lumen is divided by aweb 372 into two channels, an inlet channel 374 and an outlet channel376. The shaft has inlet orifices 377, 378, 379 communicating betweenthe inlet channel and the interior of the balloon at the distal portionof the balloon. The shaft also has outlet orifices 380, 381, 382communicating between the interior of the balloon and the outletchannel. A plug 384 is inserted in the outlet channel between the inletand the outlet orifices. The web 372 may be removed from the shaftbetween the plug and the inlet orifices to reduce resistance to flow ofthe heat exchange fluid in this portion of the shaft. Alternatively, inan embodiment not illustrated here, a tube with an open round lumen maybe spliced between the plug in the outlet channel and the inlet orificesto provide a channel under the balloon for relatively unobstructed flowof the heat exchange fluid.

The balloon may be made of, for example, a single sheet of collapsiblethin plastic material 285 sufficiently thin to allow for effectivethermal exchange between a heat exchange fluid on the interior of theballoon and blood flowing over the exterior of the balloon. Tacking thematerial to the shaft as shown at 286 may form lobes of the balloon.Tacking the sheet of plastic to itself in appropriate locations as shownat 287 and 288 may further shape the lobes. The lobed shape of theballoon surface provides for significant surface for heat exchange whileproviding for continued flow past the balloon through the space betweenthe lobes of the balloon.

In use, heat exchange fluid (not shown) may be pumped under mildpressure into the inlet channel 374. The heat exchange fluid may be, forexample, sterile saline or other biocompatible fluid with appropriateheat transfer characteristics. The heat exchange fluid flows down theinlet channel until it reaches the inlet orifices 377, 378, 379 at thedistal end of the balloon. The fluid flows from the inlet channel intothe interior of the balloon. It then flows in a proximal directionthrough the interior of the balloon until it reaches the outlet orifices380, 381, 382 at the proximal end of the balloon. The heat exchangefluid then flows from the interior of the balloon through the outletorifices and into the outlet channel 376 where it then flows back downthe shaft and out of the body.

In the manner described above, a heat exchange fluid may be circulatedthrough the balloon and either give off heat if the fluid is hotter thanthe blood flowing past the balloon, or absorb heat from the heatexchange fluid is cooler than the blood.

FIGS. 18A-E provide illustrations of another variation of the inventionheat exchange catheter 390 formed with a sleeve having an inner fluidpassageway 392 that provides regionally confined thermal transfer. Theheat transfer catheter 390 may comprise a blood channeling sleeve 394for placement within a fluid-containing body region, the sleeve definedby a proximal region 396 and a distal region 398 formed with an innerfluid passageway 392 defined by at least one relatively proximal opening395 and at least one relatively distal opening 399 each in communicationwith the fluid-containing body region for directing the flow of fluidwithin the catheter body 394. A heat exchanger is internally positionedwithin at least a portion the sleeve for regionally confined heattransfer with fluid within the inner fluid passageway 392 of the bloodchanneling sleeve. In FIGS. 18A-E the heat exchanger illustrated is afluted closed-loop exchanger positioned around the circumference of theinterior passageway 392 for circulation of heat exchange fluid asdescribed in greater detail below.

As shown in FIG. 18A, the temperature regulating catheter 390 may bepositioned within at least a portion of the aorta 364 and a blood vessel399 branching off the aorta to direct blood to the brain region. Thecatheter is positioned in the innominate artery, but could equally bepositioned, for example, with its distal portion in the right commoncarotid artery, the left common carotid, the right internal carotid andthe left internal carotid among other locations. Blood may therefore bedirected into the brain region while passing the heat exchangerpositioned within the inner fluid passageway 392 of the catheter body394. When the heat exchanger is configured for cooling blood flowingthrough the inner passageway 392 and the catheter is positioned as shownin FIG. 24A, localized hypothermia of the brain region may beeffectively achieved. The temperature regulating catheter 390 may bealso selected for applicable methods for controlling the temperature ofother selected fluid-containing body regions, for example, where thecatheter is positioned to selectively direct blood to those regions.

As illustrated in greater detail in FIGS. 18 B-G, the catheter may beformed with a proximal shaft 400, the proximal shaft having a centralworking lumen and two arc-shaped lumens in side-by side configuration.The two lumens comprise an inlet lumen 402 and an outlet lumen 403. Theblood channeling sleeve is attached to the proximal shaft at a proximalattachment region 404. The sleeve comprises a layer 405 of very thinmaterial such as a PET sheet formed into a large tube-likeconfiguration. The catheter shaft is positioned down the inside of thetube, and the sheet is attached along both the top 406 and the bottom407 of the catheter shaft along the length of the sleeve. This createstwo wing-like channels 408, 409 on each side of the catheter running thelength of the sleeve that are the inlet and outlet channelsrespectively. The outer layer of the plastic sheet of each of thesechannels may be connected together at the top of the channels 410 toform the tube-like structure that forms the sleeve. In addition, the twolayers of plastic sheet that form each channel may be connected togetherat various points or along lines 411 along the length of the sleeve toform pleats 412, and the inner layer 405 may be loose so that thechannels will billow when inflated.

At the proximal end of the sleeve, just distal of the attachment region404, an orifice 415 is formed between the inlet lumen 402 and the inletchannel of the catheter shaft 409, and similarly an orifice 416 isformed between the outlet lumen 403 and the outlet channel 408 of thesleeve. At the distal portion of the sleeve, the inlet 409 and outlet408 channels between the plastic sheets are connected, so that there isa common space 413 shared by the two channels to allow fluid flowingdown the inlet side to be removed through the outlet side as describedin greater detail below. The catheter shaft under the sleeve may havereduced profile as illustrated in FIG. 18 B so that the sleeve formed ofthe thin plastic sheets may be folded down onto the catheter shaft andhave a suitably low profile.

As an alternative method of construction, two tubes may be used tocreate the sleeve. The catheter shaft is inserted into a large outertube, and a slightly smaller inner tube is inserted into the outer tubebut over the catheter shaft. The outer tube is sealed along its lengthon the bottom of the catheter shaft, and the inner tube is sealed alongits length on the top of the catheter shaft. The inner and outer tubesare sealed to each a line opposite the catheter shaft to form twochannels between them. The seal opposite the shaft does not extend allthe way to the distal end which functions to create the common space forcommunication between the inlet and outlet channels.

Yet another method of constructing such a device is to invert a largetube of thin plastic to create an inner passageway bounded by two layersof thin plastic, with the thin plastic layers essentially attached attheir distal end. The space between the two plastic layers forms theinlet and outlet channels. The catheter shaft may be placed within theinner passageway, and the two layers sealed to each other and to thecatheter shaft along the bottom of the catheter shaft for the length ofthe inner passageway. The two layers of plastic are also sealed to eachother along the top of the inner passageway from the proximal opening toa point just short of the distal end of the passageway. This creates aninlet channel 409 and an outlet channel 408 while leaving a common space413 at the distal end of the sleeve.

In use, heat exchange fluid (not illustrated) is introduced underpressure into the inlet lumen 402 of the proximal shaft 404. It isdirected down the shaft to the inlet orifice 415, at which point itenters the inlet channel 409 between the two layers of the plastic sheeton the inlet side. The fluid is then directed down the inlet channel,essentially inflating the billowing pleats of the sleeve somewhat. Thefluid enters the common space 413 at the distal end of the bloodchanneling sleeve, and thereby enters the outlet channel 408 formedbetween the layers of plastic sheet on the outlet side of the sleeve.The fluid travels back down the length of the sleeve through the pleatedchannel to the outlet orifice 416 formed between the outlet channel 408and the outlet lumen 403 in the catheter shaft. The fluid then travelsdown the outlet channel and out of the body. In this way, heat exchangefluid may be circulated through the structure to create heat exchangebetween blood flowing through the inner passageway in heat exchangeproximity with the heat exchange fluid.

The formation of the inner passageway using a thin plastic sheets allowsblood channeling sleeve to be collapsed to a low profile, for example,wrapping or folding it onto the reduced profile portion of the cathetershaft. This in turn provides a low profile device for insertion into thevascular system. When inflated by circulating heat exchange fluid, thebillows created by the pleating of the plastic sheet increases thesurface area for heat exchange between the heat exchange fluid flowingin the catheter body and blood or other body fluid in heat exchangeproximity within the interior passageway.

In another embodiment, as illustrated in FIG. 19, a heat transfercatheter 420 may have a catheter body 422 formed as a blood channelingsleeve forming an inner passageway 423 with a heat exchanger such as aheat exchange balloon catheter 424 positioned within the innerpassageway 423. The heat exchanger may be any suitable heat exchanger,but in the embodiment shown the heat exchanger is a heat transferballoon catheter, for example the type described in the previoussections or depicted in FIG. 17B or FIG. 24A below. The heat exchangershould be suitably sized and configured to provide sufficient heatexchange capabilities but allow adequate flow of fluid through the innerpassageway.

The blood channeling sleeve has a proximal section 426 having a proximalopening 428. The wall of the sleeve in the proximal section mayadditionally form orifices 430 to further enhance perfusion of fluidfrom the surrounding body portion into the inner passageway.

The sleeve further has an intermediate section 432. The wall of thesleeve in the intermediate section is generally solid so that itgenerally will not permit fluid to exit the inner passageway through thewall of the sleeve in the intermediate section. The wall of the sleevein the intermediate and indeed throughout its length, may be formed of amaterial with thermal insulation properties to thermally insulate fluidwithin the inner passageway from the tissue such as blood outside of theinner passageway. Thus fluid entering the inner passageway at theproximal section will be channeled through the intermediate section tothe distal section 434 of the blood channeling sleeve.

The distal section 434 of the blood channeling sleeve has a distalopening 436. Further, the wall of the blood channeling sleeve at thedistal section may form orifices 438 that further enhance the flow offluid out of the inner passageway and into the surrounding body portionsuch as a blood vessel. The distal end of the sleeve 436 may be proximalof the distal end of the heat exchanger 440, may be co-extensive withthe end of the heat exchanger (not shown) or may extend distal of theheat exchanger as is shown in FIG. 26.

Additionally, there may be a central working lumen 442 that extends fromthe proximal end of the catheter shaft outside the patient's body to thedistal end of the catheter shaft 443. The central lumen may extend pastthe distal end of the heat exchange balloon or even past the distal endof the sleeve. The working lumen may be used to accommodate a guide wireor to inject dye or insert a microcatheter for additional proceduressuch as lysing a clot or performing injections through the microcatheteror any of the other uses for the working lumen as described above,particularly in reference to the working lumen shown in FIG. 17. It willreadily be appreciated that any of the above uses of the working lumenmay be performed before, after, or even during the cooling of bloodwithin the blood channeling sleeve. It may be one advantage of acatheter of the invention having a working lumen that the working lumenmay be used for any of the above purposes at the same time that coolingis taking place and without inhibiting the cooling function of thecatheter.

In use, the heat transfer catheter is placed in a fluid containing body,for example, as illustrated in FIG. 19, the arterial system. Theproximal end of the blood channeling sleeve may be, for example, locatedin the descending aorta 446. The distal end of the catheter body ispositioned as desired, in the case illustrated, in the left commoncarotid artery 448, which delivers blood to the brain. The pressuredifferential between the aorta at the level of the proximal end of thesleeve and the left common carotid artery at the distal end of sleeve issufficient to cause blood to flow through the sleeve, into left commoncarotid artery and thence to the brain. In the case illustrated, bloodenters the inner passageway of the blood channeling sleeve located inthe aorta, and travels through the inner passageway and in heat exchangeproximity with the heat transfer balloon 424 in which heated or cooledheat exchange fluid is circulating. The blood is thus heated or cooled.

The heated or cooled blood is then channeled out the distal end of theinner passageway where it flows into the left common carotid artery. Ifthe heat exchanger is cooling the blood, cooled blood would thus bedirected into the left common carotid and bath the brain in cooledblood. This, in turn, if maintained for a sufficient length of time, mayresult in regional cooling of the brain tissue with the advantages ofthat condition noted above.

It should be noted that the placement of the proximal opening of theblood channeling sleeve 423 down the descending aorta some distance fromthe aortic arch 447 will provide for a longer path for the blood totravel over the heat exchange balloon catheter in reaching the rightcommon carotid than would be the case if blood were captured anddirected through the inner passageway by a blood channeling sleevelocated entirely within the left common carotid artery. This longer flowpath provides for increased cooling effect relative to the shorter path.

Also, the placement of the blood channeling sleeve at least partially inthe aorta provides for the use of a larger heat exchanger, for example aheat exchange balloon of greater diameter, than would be possible if theheat exchange portion of the catheter body was located in the rightcommon carotid artery since the aorta is significantly larger indiameter than the right common carotid artery.

The distal section 434 of the blood channeling sleeve may also form arelatively tight fit around the blood vessel in which it is located. Inthis way, the pressure differential between the proximal and distal endof the sleeve is maximized, and essentially all the blood flowing from,for example, the aorta to the carotid artery passes through the innerpassageway and is heated or cooled by the heat exchanger. The wall ofthe blood channeling sleeve may form an occlusive shoulder to facilitatethe sealing of the artery. The heat exchanger is, for example, a heattransfer balloon that holds the walls of the catheter body extended, andthe heat exchange balloon has fins or the like that will permitsignificant blood flow between the heat exchange balloon fins andbetween the inner walls of the inner passageway and the balloon, most ifnot all the blood entering the right common carotid artery would passover the heat exchanger and thus is treated by heating or cooling.

Another embodiment of the heat transfer catheter of the invention isillustrated in FIG. 20. The catheter 450 may be provided with a bloodchanneling sleeve 452 for the receipt and direction of body fluid suchas blood. The sleeve may be essentially funnel shaped, having a distalregion 454 that is significantly larger in diameter than its distalregion 456. In this manner, the exterior surface of the blood channelingsleeve may form an occlusive shoulder that may be pressed or restagainst appropriate anatomical structures such as the interior of theartery in question, so that most or virtually all of the blood enteringthe artery in question is directed through the interior passageway 464of the blood channeling sleeve before entering the artery. In theexample illustrated, the artery into which the catheter body is insertedis the left common carotid artery, but it may be readily appreciated bythose of skill in the art that the distal portion of the bloodchanneling sleeve may be configured for similar placement in otherdesired locations.

The distal region may be elongate with a substantially cylindrical shapeand terminate in a distal opening 458. Likewise, the proximal region mayhave a proximal opening 460 which may have a valve 462 for opening orclosing the proximal opening or otherwise controlling entrance of theblood to the interior passageway 464 within the catheter body.

The interior of the proximal region 454 contains a heat exchanger. Theheat exchanger depicted is a series of spiral fins 466 which may containcontains heat transfer balloons or balloon lobes for circulating heattransfer fluid. Alternatively the fins may be other types of heating orcooling mechanisms such as electric resistance heaters.

The heat transfer catheter may be provided with a catheter shaft 468which may be provided with a working lumen 470 which may extend out ofthe patient's body when the heat exchange catheter is in place, and thusprovide for the injection of drugs, fluoroscopic dye, or the like, andmay accommodate a guide wire 472 for the placement of the heat transfercatheter. The shaft may also have channels (not shown) for the flow ofheat transfer fluid, or contain electrical wires (not shown) to connectto the heat exchangers or sensors (also not shown) on the catheter.

In use, the heat transfer catheter 450 is placed in the desired bodylocation. In the illustration of FIG. 20 the catheter is placed so thatthe proximal portion of the blood channeling sleeve 454 is within theaorta 474 and the distal portion 456 is within the left common carotidartery 476. Blood flows down the aorta (illustrated with the arrowslabeled AF@) and may enter the proximal opening 460 of the catheter bodyif the valve 462 is open. The pressure differential between the blood inthe aorta and the blood in the left common carotid is sufficient tocause the blood to flow up the inner passageway. As the blood flows upthe inner passageway it passes in heat exchange proximity with the heatexchange fins 466 and is heated or cooled. The heated or cooled blood ischanneled into the left common carotid by the blood channeling sleeve,and ultimately the heated or cooled blood baths the brain. If maintainedfor a sufficient length of time this may result in regionally heating orcooling of the brain.

Another embodiment of the heat transfer catheter of the invention isillustrated in FIG. 21. The catheter 490 illustrated in that drawing isprovided with a blood channeling sleeve 492 that is configured forplacement in the blood vessels of the patient's body, for example themain arteries leading to the brain region 494.

The blood channeling sleeve is essentially cylindrical in shape, but mayhave a slightly enlarged proximal section 496 that creates a shoulder inthe catheter body that may act as an occlusive shoulder 498 when theblood channeling sleeve is placed in an artery, such as an arterybranching off the coronary arch.

The blood channeling sleeve is shaped as a tube and forms an innerpassageway 500 that extends from the proximal section 496 that beginswith a proximal opening 502 to the distal end which terminates at adistal opening. 504. A heat exchanger such as a fined balloon heatexchange catheter 506 as described and illustrated in FIGS. 17 B and 24A is located in the catheter body and may be contained entirely withinthe inner passageway 500 of the sleeve. The fins 508 provide for addedheat transfer surface relative to a cylindrically shaped heat exchangeballoon, and also create flow channels between the fins for the flow ofblood from the proximal opening, over and between the fins of the heatexchange balloon, and out the distal end of the inner passageway. Acatheter shaft 509 may also be provided as described in conjunction withthe other embodiments described above.

FIGS. 21B-D illustrate the operation of a control system to regulate theopening and closing of a valve assembly 460 that may be formed along anysection of the sleeve 492 such as at the proximal opening 502 in orderto control the flow of blood within the inner passageway 500. Forexample, a bi-leaflet valve 510 may be positioned at the proximalopening of the sleeve 492 around the catheter shaft.

The valve 510 may have at least one closed position as shown in FIG. 21Band at least one open position as shown in FIG. 21C. Other valves suchas one-way valves may be selected for the catheter body, and the valvemay be opened and closed to a variable degree to control the amount offluid passing through the sleeve at selected points in time.

The valve 510 may be synchronously opened and/or closed in accordancewith the heartbeat of a patient as illustrated by the graph of FIG. 21D.Because aortic blood flow (L/min) is pulsatile and fluctuates atdifferent time intervals during the heartbeat cycle, a valve may beselectively opened when a relatively large amount of blood is releasedfrom the heart. At the same time, the valve may be selectively closed toretain the blood within the inner passageway 500 when the blood flow isslower. Alternatively, the valves may be controlled to cause blood toflow more slowly through the inner passageway to allow for all the bloodpassing in to the artery distal of the catheter body flows slowly overthe head exchanger for maximum heating or cooling.

As described above, a catheter control unit may simultaneously monitorbody conditions or sensed stimuli such as the heart rate, temperature atvarious locations, and pressure within the apparatus or within thepatient. When the valve 510 is in a closed position (FIG. 21B), blood orfluid is retained within the inner passageway 500 and effectively cooledby the internally positioned heat exchanger 506. A valve in a closedposition may prevent or minimize backflow of cooled fluid away from thebrain. After the blood is allowed to cool, when the heart begins to sendmore blood in the direction of the heat transfer catheter, the valve maybe activated to assume an open position (FIG. 21C) to allow the cooledblood to be pushed out of the confined cooling area by the relativelywarmer incoming blood.

When the pressure or surge of blood from the heart subsides thereafter,the valve 510 may again close, and this cooling and pumping cyclecontinues repeatedly until the desired level of regional hypothermia inthe brain is achieved. FIG. 21D is a graphic representation of the cyclejust described.

Although many of the embodiments of the invention described thus far areillustrated as either a cooling apparatus or a heating apparatus, itshould be understood that any combination of these variations may form aseries or a network of thermoregulating devices. For example, as shownin FIG. 22, a heat exchange catheter 520 includes a heat transferballoon 524 with a plurality of collapsible cooling fins 522 placed inthe aortic 526 region. A suitable heat transfer balloon catheter withfins has been previously described. The heat exchange catheter may beprovided with a catheter shaft 528. The heat exchange catheter may havea heating element 530 formed at a different location along the cathetershaft than the cooling balloon 524. The shaft 528 may include a pair oflongitudinal fluid paths (not shown) for circulating hot heat transfermedium to the heating element as well as an additional pair of fluidpaths (not shown) that circulate cold heat transfer medium to thecooling balloon 522. Alternatively, the heating fin 530 may include aresistance heater or other heating elements known in the art. In thecase of a resistance heating element, electrical current may passthrough wires within the shaft (not shown) to the heat-generatingelement.

The cooling balloon 522 may include an insulated underside 534. Bloodflowing in a certain direction, for example to the brain region, maythus be preferentially cooled relative to blood flowing to other areasof the patient's body, for example to the lower body. In the exampleillustrated in FIG. 22, the heat transfer region includes a curvedcooling balloon that is thermally insulated along the inner radius ofits curvature and thermally conductive along its outer radius of itscurvature. The cooling balloon may be placed in the aortic arch. Bloodis pumped by the heart into the aorta (indicated by arrows F) and someflows over the top surface 523 of the cooling balloon 522 in heatexchange proximity to the balloon surface. This blood is cooled, and thecool blood then flows naturally to the brain region. Blood flowing pastthe inner, insulated curvature of radius 525 is not cooled, and thusblood of normal temperature flows down the aorta and to the lower body.It may be noted that, in the example illustrated, cool blood flows tothe brain region through all of the arteries extending from the aorticarch without the need to cannulate each of those arteries. In such aconfiguration, it is also unnecessary to provide the heat transfercatheter with a blood channeling sleeve since the directional cooling isobtained without using the catheter to direct the cool blood to specificarteries.

As described, heating and cooling mechanisms may be formed at variouslocations along the shaft 528 of the heat transfer catheter 524.Alternatively, multiple heating and cooling catheters may be used incombination or cooperatively. As previously described, a common cathetercontrol unit may monitor and control multiple devices individually orcollectively, and may be responsive to one or more sensors (not shown)such as pressure sensors or temperature sensors.

Another aspect of the invention is illustrated in FIG. 23 whereby heatedor cooled blood may be directed to a specific location such as a tumor,or organ such as the heart, through a relatively small vessel. A heattransfer catheter 550 is provided having a blood channeling sleeve 552,which sleeve has a proximal opening 554 and a distal end section 552. Aheat exchanger 558 which may be, for example, a finned heat transferballoon as described above, is located within the blood channelingsleeve. The heat transfer catheter has a catheter shaft 560, whichextends from at least the interior of the blood channeling sleeve to adistal end 562.

The distal section of the sleeve is sealed around the catheter shaft564. The catheter shaft 560 has a perfusion lumen 566 extending betweenblood inlet orifices 568, 570 formed in the catheter shaft at a pointwithin the blood channeling above, and the distal end 562 of the shaft.The blood inlet orifices provide fluid communication between theperfusion lumen and the interior 572 of the blood channeling sleeve.

In use, the heat transfer catheter 560 is placed into a patient'svasculature, for example the aorta 574, and is positioned so that thedistal end 562 of the catheter shaft 560 in a desired location, forexample, in the coronary ostium. The pressure differential between theblood in the aorta at the proximal end of the blood channeling sleeve552 and the distal end 566 of the catheter shaft causes blood to flowthrough the proximal opening of the sleeve, through 554 the innerpassageway and in heat transfer proximity to the heat exchanger at whichtime the blood will be heated or cooled, and into the blood inletorifices through the central lumen of the catheter shaft and out thedistal tip of the central lumen 578. In this way, a stream of heated orcooled blood may be directed to a specific organ or tissue, for examplethe heart or tumor, and bath that organ or tissue in the heated orcooled blood. If a sufficient portion of the organ or tissue's bloodsupply is treated in this manner for a sufficient time, regional heatingor cooling of the organ or tissue in question will result.

The central lumen may extend from the distal tip 578 to a proximalopening outside the body. In this way the central lumen may function asa working lumen for all applications as previously described includingangiography and acting as a guide catheter for angioplasty. The centralor working lumen may be sized to function as a guide catheter and allowsimultaneous insertion of an angioplasty catheter and infusion of coldblood through the central or working lumen.

An alternative construction to the heat exchange balloon as illustratedin FIG. 17 is shown in FIG. 24A wherein the heat exchange region isformed using a series of three collapsible balloon lobes 902, 904, 906located around a central collapsible lumen 908. A proximal shaft 910 isformed having two channels, an inlet channel 912 and an outlet channel914. The interior of the shaft is divided into two lumens by webs 916,917, but the lumens do not occupy equal portions of the interior of theshaft. The inlet channel occupies about ⅓ of the circumference of theinterior, the outlet channel occupies about ⅔ of the circumference ofthe interior for reasons that will be explained below.

At the heat exchange region of the catheter, a transition 915 is formedbetween the shaft 910 and the tube 911 forming the central collapsiblelumen 908. The outlet channel is plugged 917, the tube 911 is affixedover the shaft 910 by, for example gluing, at the transition 915, andthe shaft ends with the tube (not shown).

In this way, as shown in FIG. 24C, the inlet channel in this portion ofthe catheter occupies the entire circumference of the shaft. At thedistal end of the balloon, inlet orifices 918, 920, 922 are formedbetween the inlet channel and the three collapsible balloons. At theproximal end of the heat exchange region, outlet orifices 924, 926, 928are formed between the interior of each balloon and the outlet channelin the shaft. As may be seen in FIG. 30D, the configuration of theoutlet channel is such that communication with the interior of each ofthe three balloons is possible.

As may be appreciated, heat exchange fluid (not shown) may flow down theinlet channel in the shaft 912, continue down lumen 908 to the distalend of the heat exchange region, exit the lumen through the inletorifices 918, 919, 920 to the interior lumens of the balloon lobes 919,921, 923, travel back down each of the three balloons and re-enter theshaft through the outlet orifices 924, 926, 928 and then down the outletchannel 914 toward the proximal end of the catheter. In this way heatexchange fluid may be circulated through the three balloons to add heatto the blood flowing in heat transfer proximity to the balloons if theheat exchange fluid is warmer than the blood, or to remove heat from theblood if the heat exchange fluid is cooler than the blood. The materialfrom which the balloons are made is made of a material that will permitsignificant thermal exchange between the heat exchange fluid on theinterior of the balloon and the body fluid such as blood flowing in heatexchange proximity to the surface of the balloon. One such appropriatematerial is very thin plastic material, which may also be made strongenough to withstand the pressure necessary for adequate flow of the heatexchange fluid.

It may also readily be appreciated that the same heat exchange balloonof the type described here and in conjunction with FIG. 17 may be usedto add heat to the blood stream or remove heat from the blood streamdepending on the relative temperature of the heat exchange fluid and theblood flowing in heat exchange proximity to the balloon. That is, thesame device at the same location may be used alternately to add or toremove heat merely by controlling the temperature of the heat exchangefluid within the device.

A heat exchange device may also be supplied as a kit comprising the heatexchange device and a set of instruction for using the heat exchangedevice. The heat exchange device may comprise, for example, a heatexchange catheter as described in this application. The instructions foruse will generally instruct the user to insert the heat exchange deviceinto a body fluid containing region and to establish the temperature ofthe heat exchange device to affect the temperature of the body fluid.The instructions for use may direct the user to heat or cool the bodyfluid to achieve any of the purposes described in this application.

While all aspects of the present invention have been described withreference to the aforementioned applications, this description ofvarious embodiments and methods shall not be construed in a limitingsense. The aforementioned is presented for purposes of illustration anddescription. It shall be understood that all aspects of the inventionare not limited to the specific depictions, configurations or relativeproportions set forth herein which depend upon a variety of conditionsand variables. The specification is not intended to be exhaustive or tolimit the invention to the precise forms disclosed herein. Variousmodifications and insubstantial changes in form and detail of theparticular embodiments of the disclosed invention, as well as othervariations of the invention, will be apparent to a person skilled in theart upon reference to the present disclosure. It is thereforecontemplated that the appended claims shall cover any such modificationsor variations of the described embodiments as falling within the truespirit and scope of the invention.

What is claimed is:
 1. A method for heating or cooling at least aportion of the body of a subject using a heat exchange catheter systemthat comprises i) a closed loop heat exchange catheter having a heatexchange region and a distal end, ii) an extracorporeally situated heatexchanger connected to the closed loop heat exchange catheter, iii)apparatus for heating or cooling heat exchange fluid that circulatesthrough the heat exchanger and through the heat exchange catheter; iv) apump for circulating the heat exchange fluid through the heat exchangerand through the heat exchange catheter thereby causing heating orcooling the heat exchange region of the catheter; v) a controller whichcontrols the temperature of the heat exchange region of the catheter andvi) a temperature sensor is used to sense a patient body temperature andvii) a user interface whereby a user may enter a target patienttemperature, said method comprising the steps of: A) connecting to thesystem a reservoir or fluid bag that contains heat exchange fluid; B)causing heat exchange fluid to flow from the reservoir or fluid bag intothe heat exchange catheter system; C) inserting the closed loop heatexchange catheter into the subject's body so that its heat exchangeregion and distal end are positioned within the subject's vasculature;D) using the pump to circulate the heat exchange fluid through theextracorporeally situated heat exchanger and the closed loop heatexchange catheter; and E) using the apparatus for heating or cooling toheat or cool the circulating heat exchange fluid, thereby heating orcooling the heat exchange region so as to cause heating or cooling ofblood that flows in heat exchange proximity to the heat exchange regionand resultant heating or cooling of at least a portion of the subject'sbody; and F) entering a target temperature via the user interface;wherein the controller is programmed to receive an indication of thesensed temperature from the temperature sensor and to cause the heatexchange catheter system to switch back and forth between the activestate and the inactive state so as to maintain the sensed temperaturebetween an upper variance set point that is above the target temperatureand a lower variance set point that is below the target temperature. 2.A method according to claim 1 wherein the heat exchange region of thecatheter expands during performance of the method.
 3. A method accordingto claim 1 wherein the heat exchange region of the catheter does notexpand during performance of the method.
 4. A method according to claim1 wherein the heat exchange fluid is circulated through theextracorporeally situated heat exchanger in a first direction and bloodflows through the vasculature in heat exchange proximity to the heatexchange region in a second direction, said second direction beingopposite said first direction.
 5. A method according to claim 1 whereinthe closed loop heat exchange catheter further comprises a working lumenhaving an outlet opening located within the subject's vasculature andwherein the method further comprises the step of infusing a substancethrough that lumen and out of the outlet opening.
 6. A method accordingto claim 5 wherein the substance is selected from the group ofmedicaments consisting of: a thrombolytic agent; an anticoagulant; aneuro-protectant; a barbiturate; a anti-seizure agent; an oxygenatedperfusate; a vaso-dilator; an agent which prevents vaso-spasm; aradiographic contrast agent; an agent to prevent platelet activation;and, an agent to deter the adhesion of platelets.
 7. A method accordingto claim 1 wherein the closed loop heat exchange catheter furthercomprises a working lumen having an outlet opening located within thesubject's vasculature and wherein the method further comprises the stepof delivering an apparatus through that lumen and out of the outletopening.
 8. A method according to claim 7 wherein the apparatus passedthrough the lumen and out of the outlet opening is selected from thegroup consisting of: a therapeutic device; a diagnostic device; anangioplasty catheter; an embolectomy catheter; an occlusion memberdelivering catheter; an embolization member delivering catheter; anelectro-cautery device; an angiographic catheter; a sensor; and, amicrocatheter.
 9. A method according to claim 1 wherein the heatexchange region of the catheter cools blood flowing in heat exchangeproximity to it with a power of 150 to 350 Watts.
 10. A method accordingto claim 1 wherein the extracorporeally situated heat exchanger has aserpentine flow path through which the heat exchange fluid iscirculated.
 11. A method according to claim 10 wherein theextracorporeally situated heat exchanger comprises a disposable heatexchanger component.
 12. A method according to claim 1 wherein the pumpcomprises a disposable pump head assembly and a reusable pump driveassembly.